On April 23, Nature Biotechnology published the research results of circular RNA aptamers in a mouse model of psoriasis completed by Chen Lingling's research group of the Center for Excellence and Innovation in Molecular Cell Science of the Chinese Academy of Sciences online. This study optimized a new method for RNA self splicing into loops, synthesized low immunogenicity circular RNA aptamers on a large scale, and achieved intervention therapy of circular RNA aptamers in a mouse model of inflammatory disease related to PKR abnormal activation, psoriasis.
Focusing on cutting-edge research on RNA has expanded human understanding of the laws of life and given rise to a series of biomedical technologies based on RNA. Circular RNA is a collective term for a series of single stranded, covalent, and closed-loop RNA molecules. In recent years, research has found that circular RNAs generally express specific pathways and patterns of generation, processing, degradation metabolism, and functional expression. Compared to linear RNA, circular RNA has the characteristics of high stability, special folding, and low immunogenicity, making it potentially valuable for biomedical applications such as being modified into novel RNA aptamers and protein translation carriers. The use of circular RNA for intervention therapy and in vivo safety assessment in disease animal models is crucial for future biomedical applications based on circular RNA.
This study achieved large-scale synthesis of low immunogenicity circular RNA aptamers (ds cRNAs) with special double stranded structures by optimizing a new method of RNA self splicing into loops. At the single-molecule level, the mechanism of interaction between ds cRNAs and PKR was elucidated using a single-molecule total internal reflection fluorescence microscope. The binding of PKR to ds cRNAs exhibits a stable binding mode with a long duration and low dissociation, indicating that ds cRNAs provide a more suitable spatial conformation for PKR binding and limit their dissociation.
The team established a stable mouse model of overexpressing circular RNA. The widespread expression and normal growth of circular RNA in various tissues demonstrate its safety. At the same time, this study achieved the intervention treatment of psoriasis in a mouse model of inflammatory disease related to PKR abnormal activation through targeted delivery of circular RNA aptamers, laying a theoretical foundation and providing technical basis for the development of novel drugs for circular RNA.
In addition, the team found in another study that delivering circular RNA aptamers through adenovirus related viral vectors can alleviate symptoms such as neuroinflammation and memory loss in a mouse model of Alzheimer's disease.
The research work was funded by the National Natural Science Foundation of China, the Ministry of Science and Technology, the Chinese Academy of Sciences and the Shanghai Municipal Science and Technology Commission, and was supported by the molecular biology technology platform, cell analysis technology platform and animal experiment technology platform of the Molecular Cell Excellence Center.
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